title: Pharmacological action of choline and aspirin coadministration on acute inflammatory pain.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain but undesirable side effects limit their clinical usefulness. Choline is a α7 nicotinic receptor agonist that has antinociceptive effects in a variety of pain models. Drug combination is a strategy in the management of pain to reduce side effects. The aim of the study was to evaluate the nature of the interaction between choline and aspirin in two distinct inflammatory pain models. The analgesic mechanism of choline was also investigated. In the writhing test, intravenous administration of choline or aspirin showed dose-dependent antinociceptive activity, and isobolographic analysis revealed a synergistic nature of the interaction between choline and aspirin. More importantly, coadministration choline with aspirin could significantly shorten the antinociceptive latency of aspirin and prolong the antinociceptive duration of aspirin in the writhing test. In the carrageenan test, single administration of choline or aspirin significantly attenuated carrageenan-induced thermal hyperalgesia in a dose-dependent relationship. Coadministration of non-analgesic doses of aspirin with choline significantly suppressed the thermal hyperalgesia, with a longer duration efficacy. Furthermore, we found that α7 nicotinic, muscarinic, and opioid-receptors are involved in the antinociceptive effect of choline in the writhing test and the antinociceptive effect produced by systemically administered choline may be via a peripheral mechanism. In conclusion, coadministration of choline and aspirin holds promise for development as a safe analgesic drug combination for inflammatory pain, with a higher potency and longer duration than either aspirin or choline alone.
authors.affiliation: Thadweik Academy of Medicine, Beijing 100039, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Yong-Ping
authors.forename: Wang
authors.initials: W
authors.lastname: Jin-Da
authors.forename: Wang
authors.initials: W
authors.lastname: Ru-Huan
authors.forename: Zhao
authors.initials: Z
authors.lastname: Xiang-Di
authors.forename: Yu
authors.initials: Y
authors.lastname: Hai-Tao
authors.forename: Wang
authors.initials: W
authors.lastname: Hai
mesh_terms: D000208:Acute Disease; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D002794:Choline / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000700:Analgesics; D004338:Drug Combinations; D018722:Nicotinic Agonists; D002794:Choline; D001241:Aspirin